Grant: Operating Grant:Bringing Rare Disease Gene Therapies to Clinical Trial Readiness

Zellweger Spectrum Disorder (ZSD) is commonly caused by inherited changes in the PEX1 gene, resulting in reduced functions of peroxisomes, organelles found in all body cells. Progressive retinal degeneration leading to blindness is a major untreatable disability, and there is urgency amongst patients and families to provide a therapy that preserves vision for improved communication, learning, mobility, autonomy and employment opportunities. To address this, our group developed PEX1 gene therapy for the retina using our PEX1-deficient mouse model and achieved remarkable structural and functional improvements in the retina of treated animals. We are now poised to move this therapy towards clinical translation, using the necessary steps outlined in this proposal. Our main aims are to: (i) complete early meetings with regulatory agencies to solidify a plan for clinical translation, (ii) develop a process to manufacture our therapy in a way that can be used in humans, and (iii) complete safety studies in mice analyzing immune activation, biodistribution, and toxicity of our gene therapy vector in tissues inside and outside the eye, using multiple doses and timeframes. Completing these compulsory aims is required by regulatory agencies (Health Canada, FDA, EMA) to initiate the clinical trial application process. In parallel, we will continue our efforts to secure a successful industry partnership for human clinical trials. The information gained from our proposed research will enable this, by providing the foundational data bridging the gap between proof-of-concept and human application.